Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT

The influence of tetrakis-ethylhexyloxy groups substituted in PPV derivative for PLEDs

New electroluminescent polymer with tetrakis-alkoxy group, poly[2,3,5,6-tetrakis(2-ethylhexyloxy)-1,4-phenylenevinylene] (TEH-PPV), has been synthesized by the Gilch polymerization. In solid film state, the TEH-PPV exhibits absorption spectra with maximum peaks at 451 nm, and PL spectrum at 505-545 nm. As compared to MEH-PPV, TEH-PPV with tetrakis-ethylhexyloxy groups in phenylene unit can get shorter conjugation length, and had more blue shifted absorption and emission peaks due to steric hindrance, in spite of increasing the number of alkoxy substituents which may increase the effective conjugation length caused by the electron-donating effect. The polymer LEDs (ITO/PEDOT/polymer/Al) of TEH-PPV showed emission with maximum peaks at around 505-590 nm. Tetrakis-ethylhexyloxy groups induced very typical vibronically structured band in solid film state, since the conjugated backbone is twisted by steric hindrance. And they can enhance the internal efficiency of the conjugated polymer as emissive layer in PLED because of the restraint of inter-chain interaction by the avoidance of close packing to give decent device performance.close111

Novel 4,7-Dithien-2-yl-2,1,3-benzothiadiazole-based Conjugated Copolymers with Cyano Group in Vinylene Unit for Photovoltaic Applications

Two novel conjugated copolymers utilizing 4,7-dithien-2-yl-2,1,3-benzothiadiazole (DTBT) coupled with cyano (-CN) substituted vinylene, as the electron deficient moeity, have been synthesized and evaluated in bulk heterojunction solar cell. The electron deficient moeity was coupled with carbazole and fluorene unit by Knoevenagel condition to provide poly(bis-2,7-((Z)-1-cyano-2-(5-(7-(2-thienyl)-2,1,3-benzothiadiazol-4-yl)-2-thienyl-ethenyl)-alt-9-(1-octylnonyl)-9H-carbazol-2-yl-2-butenenitrile) (PCVCNDTBT) and poly(bis-2,7((Z)-1-cyano-2-(5-(7-(2-thienyl)-2,1,3-benzothiadiazol-4-yl)-2-thienyl)ethenyl)-alt-9,9-dihexyl-9H-fluoren-2-yl) (PFVCNDTBT). The optical band gaps of PCVCNDTBT (1.74 eV) and PFVCNDTBT (1.80 eV) are lower than those of PCDTBT (1.88 eV) and PFVDTBT (2.13 eV), which is advantageous to provide better coverage of the solar spectrum in the longer wavelength region. The high V-oc value of the PSC of PCVCNDTBT (similar to 0.91 V) is attributed to its lower HOMO energy level (-5.6 eV) as compared to PCDTBT (-5.5 eV). Bulk heterojunction solar cells based on the blends of the polymers with [6,6]phenyl-C-61-butyric acid methyl ester (PC61BM) gave power conversion efficiencies of 0.76% for PCVCNDTBT under AM 1.5, 100 mW/cm(2).close

Potential late-onset Alzheimer's diseaseassociated mutations in the ADAM10 gene attenuate α-secretase activity. Hum Mol Genet 18

ADAM10, a member of a disintegrin and metalloprotease family, is an a-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated a-secretase activity of ADAM10 (>70% decrease), and elevated Ab levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD